In the biological field, the surface characteristics of a substrate control the functioning of that substrate relative to fluids with which the substrate surface comes in contact. Since known living organisms rely heavily on the presence of water, the hydrophilicity or hydrophobicity of a given surface plays a major role in determining whether a medical device can perform well in the environment in which it is to function. The surface of the medical device must be designed to provide biocompatibility with fluids it is to contact in the environment, and may be designed to achieve a particular interaction with the fluids it contacts. The ability of a medical device to function either in-vivo or in-vitro depends on the surface presented by the medical device. For example, with respect to an implant which is used in medical applications, the ability of the implant to integrate into the location at which it is placed and to function in combination with surrounding tissues and fluids depends significantly on the hydrophilicity or hydrophobicity of the implant surface, and frequently depends on the presence or absence on the surface of the implant of chemical compounds having particular properties. With respect to a medical device surface used for chemical analysis, for example, the device must provide a functional surface which enables the particular analytical function.
The need for biocompatible films and, in particular, for hydrophilic, neutral biocompatible surfaces that resist adhesion and growth of protein, lipids, and bacteria, drives the search for new materials compatible with medical and biological applications. For example, those skilled in the art have long recognized the need for rendering the surface of contact lenses hydrophilic in order to improve their biocompatibility or wettability by tear fluid in the eye. This is necessary to improve the wear comfort of contact lenses and/or to extend their resistance to bacterial infection, inflammation, and other adverse effects resulting from incompatibility of the lens with the human body and its functions.
In the case of contact lenses, in particular, the lens surface must be resistant to bacterial growth and infection, and must also be hydrophilic to allow for efficient binding of water by the lens and sufficient flow of oxygen to the surface of the eye. Carbohydrate type coatings are of particular interest, as they resemble the natural coating of a human cell and are less prone to inflammation and irritation of tissue due to chemical and biological incompatibility. They also have a lubricating effect caused by their high surface energy, are optically clear, and facilitate exchange of fluids between the surface of the coated device and the body.
In many applications where the wear on the coating is likely to occur due to mechanical contact or where fluid flow is to occur over the substrate surface on which the layer of coating is present, it is helpful to have the coating chemically bonded directly to the substrate surface via chemical reaction of active species which are present in the coating reactants/materials with active species on the underlying substrate surface. In addition, particular precursor materials may be selected which are known to provide particular functional moieties.
With respect to layers and coatings which are chemically bonded to a medical device surface, there are a number of areas of particular current interest. By way of example, and not by way of limitation, surface structure and exterior coatings on that surface structure may be used for biotechnology applications where the surface wetting properties and functionality are useful for analytical purposes, for controlling fluid flow and sorting of fluid components, and for altering the composition of components which come into contact with the surface, for example.
Due to the nanometer size scale of some of medical device applications which employ coatings exhibiting specialized functionality, a need has grown for improved methods of controlling the formation of the coating, including the formation of individual layers within a multi-layered coating, for example. Typically such coatings range in thickness from about 1 nm (10 Å) to about 1 micron (μ). At the present time, approximately 95% of the new applications for medical device coatings make use of a coating thickness which is less than 100 nm, with a number of applications requiring a coating thickness in the range of about 50 nm to 100 nm. Historically, surface coatings for medical devices have been applied by contacting a device substrate surface with a liquid coating material. While this technique enables efficient coating deposition, it frequently results in limited control over the surface properties of the applied coating. In the case of coating a surface of a medical device which must function on a nanometer scale, use of liquid phase processing limits device yield due to contamination and capillary forces. More recently, deposition of coatings from a vapor-phase has been used in an attempt to improve coating properties. However, the common vapor-phase deposition methods may not permit sufficient control of the molecular level reactions taking place during the deposition of surface bonding layers or during the deposition of functional coatings, when the deposited coating needs to exhibit functional surface properties on a nanometer (nm) scale.
For purposes of illustrating methods of coating formation where vaporous and liquid precursors are used to deposit a coating on a substrate, applicants would like to mention the following publications and patents which relate to methods of coating formation, for purposes of illustration. Most of the background information provided is with respect to various chlorosilane-based precursors; however it is not intended that the present invention be limited to this class of precursor materials. In addition, applicants would like to make it clear that some of this Background Art is not prior art to the present invention. It is mentioned here because it is of interest to the general subject matter.
In an article by Barry Arkles entitled “Tailoring surfaces with silanes”, published in CHEMTECH, in December of 1977, pages 766-777, the author describes the use of organo silanes to form coatings which impart desired functional characteristics to an underlying oxide-containing surface. In particular, the organo silane is represented as RnSiX(4-n) where X is a hydrolyzable group, typically halogen, alkoxy, acyloxy, or amine. Following hydrolysis, a reactive silanol group is said to be formed which can condense with other silanol groups, for example, those on the surface of siliceous fillers, to form siloxane linkages. Stable condensation products are said to be formed with other oxides in addition to silicon oxide, such as oxides of aluminum, zirconium, tin, titanium, and nickel. The R group is said to be a nonhydrolyzable organic radical that may possess functionality that imparts desired characteristics. The article also discusses reactive tetra-substituted silanes which can be fully substituted by hydrolyzable groups and how the silicic acid which is formed from such substituted silanes readily forms polymers such as silica gel, quartz, or silicates by condensation of the silanol groups or reaction of silicate ions. Tetrachlorosilane is mentioned as being of commercial importance since it can be hydrolyzed in the vapor phase to form amorphous fumed silica.
The article by Dr. Arkles shows how a substrate with hydroxyl groups on its surface can be reacted with a condensation product of an organosilane to provide chemical bonding to the substrate surface. The reactions are generally discussed and, with the exception of the formation of amorphous fumed silica, the reactions are between a liquid precursor and a substrate having hydroxyl groups on its surface. A number of different applications and potential applications are discussed.
In an article entitled “Organized Monolayers by Adsorption. 1. Formation and Structure of Oleophobic Mixed Monolayers on Solid Surfaces”, published in the Journal of the American Chemical Society, Jan. 2, 1980, pp. 92-98, Jacob Sagiv discussed the possibility of producing oleophobic monolayers containing more than one component (mixed monolayers). The article is said to show that homogeneous mixed monolayers containing components which are very different in their properties and molecular shape may be easily formed on various solid polar substrates by adsorption from organic solutions. Irreversible adsorption is said to be achieved through covalent bonding of active silane molecules to the surface of the substrate.
U.S. Pat. No. 5,002,794 to Rattier et al., issued Mar. 26, 1991, describes a method of controlling the chemical structure of polymeric films formed by plasma deposition. An important aspect of the method involves controlling the temperature of the substrate and the reactor to create a temperature differential between the substrate and reactor such that the precursor molecules are preferentially adsorbed or condensed onto the substrate either during plasma deposition or between plasma deposition steps. (Abstract) This reference discusses the immobilization of poly(ethylene glycol), also referred to as PEG or as polyethylene oxide (PEO). The application of PEG-like thin films, grafted onto a wide variety of substrates, is described as carried out using a plasma deposition apparatus. Substrates are said to be cleaned by etching with an argon plasma in some instances. An object to be treated is placed in a vacuum chamber, and reactant precursor is introduced into the chamber at a specified rate so as to maintain a constant pressure in the reactor. A power supply is used to maintain a plasma at a set power level during the deposition. The disclosure teaches that, depending on the length of time the plasma is maintained, the thickness of the deposited films may be controlled as desired. The precursor material is introduced into the reaction vessel and pressure and flow of the precursor material are stabilized, with the plasma deposition and condensation carried out simultaneously or alternately for any desired length of time. After the deposition is complete, the coated specimens may be permitted to remain in the presence of the precursor “to permit the chemical reactions in the film to go to completion”. This is referred to as a quench step. The disclosure of this reference is hereby incorporated by reference in its entirety.
Kevin L. Prime et al. published an article entitled “Self-Assembled Organic Monolayers: Model Systems for Studying Adsorption of Proteins at Surfaces” in Science 1991, 252, pp. 1164-1167. Self-assembled monolayers (SAMS) of ω-functionalized long-chain alkanethiolates on gold films are described as excellent model systems with which to study the interactions of proteins with organic surfaces. Monolayers containing mixtures of hydrophobic (methyl terminated) and hydrophilic [hydroxyl-, maltose-, and hexa(ethylene glycol)-terminated] alkanethiols are said to be tailored to select specific degrees of adsorption. The SAMS were prepared by the chemisorption of alkanethiols from 0.25 mM solutions in ethanol or methanol onto thin (200.+−0.20 nm) gold films supported on silicon wafers. The hexa(ethylene glycol)-terminated SAMS are said to be the most effective in resisting protein adsorption. (Abstract) The subject matter of this article is hereby incorporated by reference in its entirety.
In June of 1991, D. J. Ehrlich and J. Melngailis published an article entitled “Fast room-temperature growth of SiO2 films by molecular-layer dosing” in Applied Physics Letters 58 (23), pp. 2675-2677. The authors describe a dosing technique for room-temperature growth of .alpha.-SiO2 thin films, which growth is based on the reaction of H2O and SiCl4 adsorbates. The reaction is catalyzed by the hydrated SiO2 growth surface, and requires a specific surface phase of hydrogen-bonded water. Thicknesses of the films is said to be controlled to molecular-layer precision; alternatively, fast conformal growth to rates exceeding 100 nm/min is said to be achieved by slight depression of the substrate temperature below room temperature. Potential applications such as trench filling for integrated circuits and hermetic ultrathin layers for multilayer photoresists are mentioned. Excimer-laser-induced surface modification is said to permit projection-patterned selective-area growth on silicon.
An article entitled “Atomic Layer Growth of SiO2 on Si(100) Using The Sequential Deposition of SiCl4 and H2O” by Sneh et al. in Mat. Res. Soc. Symp. Proc. Vol 334, 1994, pp. 25-30, describes a study in which SiO2 thin films were said to be deposited on Si(100) with atomic layer control at 600° K (≅327° C.) and at pressures in the range of 1 to 50 Torr using chemical vapor deposition (CVD).
A. A. Campbell et al. presented a paper “Low Temperature Solution Deposition of Calcium Phosphate Coatings For Orthopedic Implants” at the American Ceramic Society Meeting, Apr. 24-28, 1994, in Indianapolis, Ind., published by NTiS, document DE94014497, which describes the growth of calcium phosphate coatings from aqueous solution onto a derivatized self-assembled monolayer (SAM) which was covalently bound to a titanium metal substrate. The SAM molecules were reported as providing an [ideal] connection between the metal surface and the calcium phosphate coating. A trichlorosilane terminus of the SAM molecule was reported as insuring covalent attachment to the substrate, while a fractionalized “tail” of the SAM molecule induced heterogeneous nucleation of the calcium phosphate coating from supersaturated solutions. (Abstract) The introduction of the article explains that bone and dental implant technology is currently inadequate. The bond between bone and implant materials (such as Ti and metal alloys) is said to fail, requiring additional surgery to remove and replace the implant after only a few years of use. To date, hydroxyapatite (HAP) coatings are said to have shown exceptional promise as bioactive coatings for metallic implant devices. It is commented that the apatite may be able to partially dissolve, intergrow, and become partially incorporated with the apatite in growing bone, forming a coating: bone interface as strong as the bone itself. The subject matter of this reference is hereby incorporated by reference in its entirety.
U.S. Pat. No. 5,328,768 to Goodwin, issued Jul. 12, 1994, discloses a method and article wherein a glass substrate is provided with a more durable non-wetting surface by treatment with a perfluoroalkyl alkyl silane and a fluorinated olefin telomer on a surface which comprises a silica primer layer. The silica primer layer is said to be preferably pyrolytically deposited, magnetron sputtered, or applied by a sol-gel condensation reaction (i.e. from alkyl silicates or chlorosilanes). A perfluoroalkyl alkyl silane combined with a fluorinated olefin telomer is said to produce a preferred surface treatment composition. The silane/olefin composition is employed as a solution, preferably in a fluorinated solvent. The solution is applied to a substrate surface by any conventional technique such as dipping, flowing, wiping, or spraying.
In U.S. Pat. No. 5,372,851, issued to Ogawa et al. on Dec. 13, 1995, a method of manufacturing a chemically adsorbed film is described. In particular a chemically adsorbed film is said to be formed on any type of substrate in a short time by chemically adsorbing a chlorosilane based surface active-agent in a gas phase on the surface of a substrate having active hydrogen groups. The basic reaction by which a chlorosilane is attached to a surface with hydroxyl groups present on the surface is basically the same as described in other articles discussed above. In a preferred embodiment, a chlorosilane based adsorbent or an alkoxyl-silane based adsorbent is used as the silane-based surface adsorbent, where the silane-based adsorbent has a reactive silyl group at one end and a condensation reaction is initiated in the gas phase atmosphere. A dehydrochlorination reaction or a de-alcohol reaction is carried out as the condensation reaction. After the dehydrochlorination reaction, the unreacted chlorosilane-based adsorbent on the surface of the substrate is washed with a non-aqueous solution and then the adsorbed material is reacted with aqueous solution to form a monomolecular adsorbed film.
Patrick W. Hoffmann et al., in an article published by the American Chemical Society, Langmuir 1997, 13, pp. 1877-1880, entitled: “Vapor Phase Self-Assembly of Fluorinated Monolayers on Silicon and Germanium Oxide” describe the surface coverage and molecular orientation of monomolecular thin organic films on a Ge/Si oxide substrate. A gas phase reactor was said to have been used to provide precise control of surface hydration and reaction temperatures during the deposition of monofunctional perfluorated alkylsilanes. Complete processing conditions are not provided, and there is no description of the apparatus which was used to apply the thin films.
Miqin Zhang et al., in an article entitled “Hemocompatible Polyethylene Glycol Films on silicon”, published in Biomedical Microdevices, 1(1), pp. 81-87 (1998), describe the functionalization of polyethylene glycol (PEG) by SiCl3 groups on its chain ends, and the reaction of the PEG organosilicon derivatives with hydroxylated groups on silicon surfaces. The reactant preparations and the attachment of PEG film onto silicon surfaces were carried out in a glass apparatus which prevented exposure to the atmosphere. Nitrogen was used as the isolation gas, and the precursor formation reactions were carried out in solutions, with attachment of the precursor to the silicon surface by contact of a precursor solution with the silicon surface.
In another article entitled “Proteins and cells on PEG immobilized silicon surfaces”, published in Biomaterials 19 (1998) pp. 953-960, Zhang et al. describe the modification of silicon surfaces by covalent attachment of self-assembled polyethylene glycol (PEG) film. Adsorption of albumin, fibrinogen, and IgG to PEG immobilized silicon surfaces was studied to evaluate the non-fouling and non-immunogenic properties of the surfaces. The adhesion and proliferation of human fibroblast and Hela cells onto the modified surfaces were investigated to examine their tissue biocompatibility. Coated PEG chains were said to show the effective depression of both plasma protein adsorption and cell attachment to the modified surfaces. The mechanisms accounting for the reduction of protein adsorption and cell adhesion on modified surfaces were discussed. (Abstract) This article is hereby incorporated by reference in its entirety, PEG was immobilized on silicon by the functionalization of a PEG precursor in the manner described in the article discussed above.
In an article entitled “Vapor phase deposition of uniform and ultrathin silanes” by Yuchun Wang et al, SPIE Vol. 3258-0277-786X/98 pp. 20-38, the authors discuss the need for ultrathin coatings on the surfaces of biomedical microdevices to regulate hydrophilicity and to minimize unspecific protein adsorption. It is recommended that silane “monolayers” which are typically formed on surfaces in organic solution, be vapor deposited instead, to reduce the formation of variable thickness films and the formation of submicron aggregates or islands on the silicon substrate surface. The vapor phase coating method is carried out at ambient pressure using nitrogen to flush out the system, and subsequently using nitrogen as a carrier gas for the reactants. (Abstract) It is mentioned that an alternative strategy consists of (applying) coating silanes in high vacuum, but no process conditions were provided. Biomedical devices formed by the method are said to be useful in the formation of microfabricated filters which regulate hydrophilicity of a surface and minimize unspecific protein absorption.
Darrel J. Bell et al., in an article entitled “Using polyethylene glycol) silane to prevent protein adsorption in microfabricated silicon channels”, SPIE Vol. 3258-0277-786X/98, pp. 134-140, describe progress toward achieving a long-term antifouling surface for use in chemical and biological agent purification and detection. Poly(ethylene glycol) (PEG) silane is covalently bonded to the hydroxyls of an oxide layer on a silicon device surface and the Pyrex cover slip. (Abstract) Patterned silicon wafers are thermally oxidized to provide an oxide layer for silanization chemistry. (Page 135) A PEG-3400 silane was dissolved in anhydrous toluene to form either a 1% or a 2% solution. Silicon and Pyrex samples were placed in stirred PRG solution for varying times (24, 4 and 1.5 hours) to deposit a layer of PEG. Subsequently, all samples underwent 2-5 minute sonicating rinses in fresh anhydrous toluene before being cured for 14 hours at a temperature of 125° C. in a vacuum under 30 in. Hg.
In an article entitled “SiO2 Chemical Vapor Deposition at Room Temperature Using SiCl4 and H2O with an NH3 Catalyst”, by J. W. Klaus and S. M. George in the Journal of the Electrochemical Society, 147 (7) 2658-2664, 2000, the authors describe the deposition of silicon dioxide films at room temperature using a catalyzed chemical vapor deposition reaction. The NH3 (ammonia) catalyst is said to lower the required temperature for SiO2 CVD from greater than 900° K to about 313-333° K.
U.S. Patent Publication No. US 2002/0065663 A1, published on May 30, 2002, and titled “Highly Durable Hydrophobic Coatings And Methods”, describes substrates which have a hydrophobic surface coating comprised of the reaction products of a chlorosilyl group containing compound and an alkylsilane. The substrate over which the coating is applied is preferably glass. In one embodiment, a silicon oxide anchor layer or hybrid organo-silicon oxide anchor layer is formed from a humidified reaction product of silicon tetrachloride or trichloromethylsilane vapors at atmospheric pressure. Application of the oxide anchor layer is followed by the vapor-deposition of a chloroalkylsilane. The silicon oxide anchor layer is said to advantageously have a root mean square surface (RMS) roughness of less than about 6.0 nm, preferably less than about 5.0 nm and a low haze value of less than about 3.0%. The RMS surface roughness of the silicon oxide layer is preferably said to be greater than about 4 nm, to improve adhesion. Too small an RMS surface is said to result in the surface being too smooth, that is to say an insufficient increase in the surface area/or insufficient depth of the surface peaks and valleys on the surface. However, too great an RMS surface area is said to result in large surface peaks, widely spaced apart, which begins to diminish the desirable surface area for subsequent reaction with the chloroalkylsilane by vapor deposition.
Simultaneous vapor deposition of silicon tetrachloride and dimethyldichlorosilane onto a glass substrate is said to result in a hydrophobic coating comprised of cross-linked polydimethylsiloxane which may then be capped with a fluoroalkylsilane (to provide hydrophobicity). The substrate is said to be glass or a silicon oxide anchor layer deposited on a surface prior to deposition of the cross-linked polydimethylsiloxane. The substrates are cleaned thoroughly and rinsed prior to being placed in the reaction chamber.
U.S. Pat. No. 5,936,703 to Miyazaki et al, issued Aug. 10, 1999 describes a specialized alkoxysilane compound or its acid-processed reaction product, which is used as a surface processing solution for a contact lense surface. The compound is said to be capable of providing hydrophilicity to the surface of various substrates which are treated with a surface processing solution of the compound. The hydrophilicity is said to be peculiar to the specialized alkoxysilane compound, whereas other silane coupling agents containing alkoxysilane groups are said to have been used to provide hydrophobic properties to the surface of inorganic or organic materials. (Abstract and Col. 1, lines 31-38.)
T. M. Mayer et al. describe a “Chemical vapor deposition of fluoroalkylsilane monolayer films for adhesion control in micro electromechanical systems” in J. Vac. Sci. Technol. B 18(5), September/October 2000. This article mentions the use of a remotely generated microwave plasma for cleaning a silicon substrate surface prior to film deposition, where the plasma source gas is either water vapor or oxygen.
U.S. Pat. No. 6,200,626 to Grobe, III et al., issued Mar. 13, 2001, describes an optically clear, hydrophilic coating produced on the surface of a silicone medical device by sequentially subjecting the surface of a lens to plasma polymerization reaction in a hydrocarbon atmosphere, to produce a carbon layer, then graft polymerizing a mixture of monomers comprising hydrophilic monomers onto the carbon layer. The invention is said to be especially useful for forming a biocompatible coating on silicone hydrogen contact lenses. (Abstract) The invention is said to be directed toward treatment of silicone medical devices. (Col. 3, lines 17-19.) Various silicon-containing monomers and a silicone hydrogel material are described, which may be used to provide a substrate. (Col. 3-Col. 6.)
Typically, the substrate surface is plasma oxidized, using a strong oxidizing plasma (Col. 8, lines 11-19), followed by plasma-polymerization deposition with a C1 to C10 saturated or unsaturated hydrocarbon to form a polymeric carbonaceous primary coating, followed by a grafting of a mixture of monomers (inclusive of macromers) onto the carbonaceous primary coating, to form a hydrophilic, biocompatible secondary coating. (Col. 7, lines 40-49.) The grafting reaction may employ an initiator, or the carbonaceous layer may be activated to promote the covalent attachment of polymer to the surface. The grafting polymer may be formed by using an aqueous solution of an ethylenically unsaturated monomer or a mixture of monomers capable of undergoing graft addition polymerization. (Col. 9, lines 18-53.)
U.S. Pat. No. 6,213,604 to Valint, Jr. et al., issued Apr. 10, 2001, describes plasma surface treatment of silicone hydrogel contact lenses. In particular, the surface of a contact lens is modified to increase its hydrophilicity by coating the lens with a carbon-containing layer made from a diolefinic compound having 4 to 8 carbon atoms. In one embodiment, an optically clear, hydrophilic coating is provided upon the surface of a silicone hydrogel lens by sequentially subjecting the surface of the lens to: a plasma oxidation reaction, followed by a plasma polymerization reaction in the presence of a diolefin, in the absence of air (in the absence of oxygen or nitrogen, where “absence” is defined to mean at a concentration of less than 10% by weight of oxygen or nitrogen, preferably less than two percent, and most preferably zero percent). Finally, the resulting carbon-containing layer is rendered hydrophilic by a further plasma oxidation reaction or by the attachment of a hydrophilic polymer chain. (Abstract and Col. 2, lines 44-53). Silicone lenses which are hydrogels can absorb and retain water in an equilibrium state. Hydrogels generally have a water content greater than about five weight percent and more commonly between about ten to about eighty weight percent. (Col. 1, lines 19-27.)
D. M. Bubb et al., in an article entitled “Vapor deposition of intact polyethylene glycol thin films”, published in Appl. Phys. A (2001) Digital Object Identified (DOI) 10.1007/s003390100884, describe the deposition of polyethylene glycol (PEG) films of average molecular weight, 1400 amu, by both matrix assisted pulsed laser evaporation (MAPLE) and pulsed laser deposition (PLD). Films were deposited on NaCl plates, Si(111) wafers, and glass slides. The MAPLE deposited films are said to have shown nearly identical resemblance to the starting material, while the PLD films did not. (Abstract) In MAPLE, the material to be deposited is dissolved in an appropriate solvent, typically at 0.1 to 2.0 wt. % concentration and is frozen solid. The composite is evaporated using a pulsed laser. The vaporized solvent is said not to form a film, and is pumped away by the vacuum system in the film deposition chamber.
V. A. Shamamian et al., in an article entitled “Mass Spectrometric Characterization of Pulsed Plasmas for Deposition of Thin Polyethylene Glycol-Like Polymer Films”, published in 2001 by the Society of Vacuum Coaters 505/856-7188, 44th Annual Technical Conference Proceedings, Philadelphia, Apr. 21-26, 2001, describe the characterization of pulsed inductively coupled rf plasmas of two organic precursor molecules, isopropyl alcohol and 1,4 dioxane using Langmuir probes and in situ mass spectrometry. The ultimate goal of the work was to develop predictable models for PECVD processes for thin polymer films with functionalized surfaces. (Abstract) Polyethylene glycol, or PEG-like structures were chosen as the target PECVD functional groups. The precursors mentioned above are precursors for a cyclic version of a diethylene glycol structure.
Daniel M. Bubb et al., in an article entitled “Resonant infrared pulsed-laser deposition of polymer films using a free-electron laser”, published in J. Vac. Sci. Technol. A 19(5), September/October 2001, pp. 2698-2702, describe the pulsed laser deposition (PLD) of thin films of polyethylene glycol (MW 1500) using both a tunable infrared (λ=2.9 pan, 3.4 μm) and ultraviolet laser (λ 193 nm). When the IR laser is tuned to a resonant absorption in the polymer, the IR PLD thin films are said to be identical to the starting material, where the UV PLD are said to show significant structural modification. (Abstract)
U.S. Pat. No. 6,475,808 to Wagner et al., issued Nov. 5, 2002, describes arrays of proteins which are used for in vitro screening of biomolecular activity. Methods of using the protein arrays are also disclosed. The protein arrays are said to be immobilized on one or more organic thin films on a substrate surface. (Abstract) A number of different methods for immobilizing the proteins are discussed. One of the methods described is the use of a self-assembled monolayer having an end group X available which provides chemisorption or physisorption of the monolayer onto the surface of a substrate. If the substrate is a material such as silicon, silicon oxide, or a metal oxide, then X may be a monohalosilane, dihalosilane, trihalosilane, trialkoxysilane, dialkoxysilane, or a monoalkoxysilane. (Col. 15, lines 31-51) The other end group of the self-assembled monolayer, Y, provides coupling with the protein readily under normal physiological conditions not detrimental to the activity of the protein. The functional group Y may either form a covalent linkage or a noncovalent linkage with the protein. (Col. 16, lines 33-49.) Particular deposition techniques for application of the self-assembled monolayer are not disclosed.
Ketul C. Popat et al., in an article entitled “Characterization of vapor deposited polyethylene glycol) films on silicon surfaces for surface modification of microfluidic systems”, in the J. Vac. Sci. Technol. B 21(2), March/April 2003 at pages 645-654, discuss microfluidic systems which employ Poly(ethylene glycol) (PEG) as a surface coating to reduce protein adsorption on microfluidic surfaces. The PEG is said to reduce protein adsorption on the microfluidic surface. The authors developed a method of vapor deposition for the PEG which is said to be helpful when the size of microfluidic surfaces is in the micro/nanoscale range. Films deposited using the vapor deposition technique are said to decrease protein adsorption by 80% and to be stable for a period of 4 weeks. (Abstract).
The authors describe the use of silanes as precursors or bridges to connect a PEG molecule to a surface. The silane precursors are described as highly sensitive to moisture, forming aggregates and lumps on a silicon surface in the presence of moisture. These aggregates are said to clog or mask micro/nano-size features on devices. The article focuses on the vapor deposition of silane and, subsequently, PEG on silicon surfaces in a moisture free nitrogen atmosphere. To deposit PEG on a surface, a basic starting molecule of ethylene oxide is used in combination with a gas catalyst. (Page 646) A substrate surface was a silicon wafer, p-type, boron doped, with (1,0,0) orientation. The silicon surface was treated with ammonium hydroxide and hydrogen peroxide in distilled water to attach an —OH group to the surface. Ethylene oxide in vapor phase was used to grow PEG on the silicon surface. The surface was first silanized with a reactive end group silane like 3-APTMS. This is a bifunctional organosilane possessing a reactive primary amine and a hydrolyzable inorganic trimethoxysilyl group. This is a short-chained silane with a boiling point of 194° C. It is said to violently react with water and to tend to polymerize on surfaces forming lumps and aggregates. Therefore the application of the silane to the silicon surface is said to be carried out in a moisture free environment to reduce the risk of formation of lumps and aggregates on the substrate surface. (Page 647)
Boron trifluoride was used as a gaseous catalyst in combination with the ethylene oxide during formation of the PEG on the silicon surface. The boron trifluoride is said to be a weak Lewis acid which accepts a free pair of electrons of —NH2 on APTMS, to make a reaction site available for a reactive ethylene oxide molecule to attach and then an additional polymerization reaction to form PEG on the substrate surface. The PEG composition is said to be controlled by the concentration of ethylene oxide and the polymerization time. The reaction is said to be terminated by flowing inert gas over the surface after an appropriate time. Nitrogen gas is used at specific flow rates through the PEG deposition chamber to maintain an inert atmosphere in the chamber. Silane is injected “in the flow loop” which is heated and maintained at a temperature a little above the boiling point of silane. Vapors of the silane are picked up by the running nitrogen. This is said to facilitate the reaction on the silicon surface to form a thin organosilane film. Nitrogen is flowed through the deposition chamber to remove unreacted silane. Ethylene oxide and boron trifluoride at a ratio of 1:2 were maintained in the reaction chamber during deposition of the PEG film. (Page 647) The disclosure of this article is hereby incorporated by reference in its entirety. More details of this work are presented in a Doctor of Philosophy graduate thesis titled: “Development Of Vapor Deposited Thin Films For Bio-Microsystems” by Ketul C. Popat, approved at the University of Illinois at Chicago on Oct. 11, 2002, the content of which is hereby incorporated by reference in its entirety.
U.S. Pat. No. 6,576,489 to Leung et al., issued Jun. 10, 2003, describes methods of forming microstructure devices. The methods include the use of vapor-phase alkylsilane-containing molecules to form a coating over a substrate surface. The alkylsilane-containing molecules are introduced into a reaction chamber containing the substrate by bubbling an anhydrous, inert gas through a liquid source of the alkylsilane-containing molecules, and transporting the molecules with the carrier gas into the reaction chamber. The formation of the coating is carried out on a substrate surface at a temperature ranging between about 15° C. and 100° C., at a pressure in the reaction chamber which is said to be below atmospheric pressure, and yet sufficiently high for a suitable amount of alkylsilane-containing molecules to be present for expeditious formation of the coating.
U.S. Patent Publication No. 2003/0180544 A1, published Sep. 25, 2003, and entitled “anti-Reflective Hydrophobic Coatings and Methods, describes substrates having anti-reflective hydrophobic surface coatings. The coatings are typically deposited on a glass substrate. A silicon oxide anchor layer is formed from a humidified reaction product of silicon tetrachloride, followed by the vapor deposition of a chloroalkylsilane. The thickness of the anchor layer and the overlayer are said to be such that the coating exhibits light reflectance of less than about 1.5%. The coatings are said to be comprised of the reaction products of a vapor-deposited chlorosilyl group containing compound and a vapor-deposited alkylsilane.
U.S. Patent Publication No. US2004/0023413 A1, of Cindra Opalsky, published Feb. 5, 2004, describes the use of polyethylene glycol, or a block co-polymer and/or derivative thereof which has been immobilized on a planar oxide surface that has been silanized. The immobilized molecule is then used in a microscale screening or binding assay in an optimal hydrogel environment (Abstract). The polyethylene glycol is typically used in the form of a “hydrogel”, where the term hydrogel refers to a gelatinous colloid or aggregate of molecules in a finely dispersed semi-liquid state, where the molecules are in the external or dispersion phase and water is in the internal or dispersed phase. Preferred hydrogels are made using polyethylene glycol, polypropylene glycol or polysine, or a derivative (such as a branched or star molecule) or block co-polymer thereof. The immobilization or coupling of a hydrogel to a surface is typically carried out by contacting the hydrogel with a surface of interest to cause a physical or chemical reaction to occur between the hydrogel and the surface via one or more linkers. For chemical attachment of the hydrogel to the surface, preferred surfaces include compositions containing oxides of silicon or tungsten. In addition, a silanized planar surface is also mentioned, where a surface having hydroxyl groups present is reacted with an organo-silane compound to create additional reactive groups for chemical coupling. Preferably, one or more linkers comprising the hydrogel are contacted with the surface by depositing an aqueous solution directly onto the surface, which optionally may contain an intermediate layer to facilitate binding. This reference is hereby incorporated by reference in its entirety.
Other known related references pertaining to coatings deposited on a substrate surface from a vapor include the following, as examples and not by way of limitation. U.S. Pat. No. 5,576,247 to Yano et al., issued Nov. 19, 1996, entitled: “Thin layer forming method where hydrophobic molecular layers preventing a BPSG layer from absorbing moisture”. U.S. Pat. No. 5,602,671 of Hornbeck, issued Feb. 11, 1997, which describes low surface energy passivation layers for use in micromechanical devices. Jian Wang et al., in an article published in Thin Solid Films 327-329 (1998) 591-594, entitled: “Gold nanoparticulate film bound to silicon surface with self-assembled monolayers”, discuss a method for attaching gold nanoparticles to silicon surfaces with a self aligned monolayer (SAM) used for surface preparation”.
Other known related references pertaining to coatings deposited on a substrate surface from a vapor include the following, as examples and not by way of limitation. U.S. Pat. No. 5,576,247 to Yano et al., issued Nov. 19, 1996, entitled: “Thin layer forming method where hydrophobic molecular layers preventing a BPSG layer from absorbing moisture”. U.S. Pat. No. 5,602,671 of Hornbeck, issued Feb. 11, 1997, which describes low surface energy passivation layers for use in micromechanical devices.
Some of the various methods useful in applying layers and coatings to a substrate have been described above. There are numerous other patents and publications which relate to the deposition of functional coatings on substrates, but which appear to us to be more distantly related to the present invention. However, upon reading these informative descriptions, it becomes readily apparent that control of coating deposition on a molecular level is not addressed in adequate detail in most instances. When this is discussed, the process is typically described in generalized terms like those mentioned directly above, which terms are not enabling to one skilled in the art, but merely suggest experimentation. To provide a monolayer or a few layers of a functional coating on a substrate surface which is functional or exhibits features on a nanometer scale, it is necessary to tailor the coating precisely. Without precise control of the deposition process, the coating may lack thickness uniformity and surface coverage, providing a rough surface. Or, the coating may vary in chemical composition across the surface of the substrate. Or, the coating may differ in structural composition across the surface of the substrate. Any one of these non-uniformities may result in functional discontinuities and defects on the coated substrate surface which are unacceptable for the intended application of the coated substrate.
U.S. patent application Ser. No. 10/759,857 of the present applicants describes processing apparatus which can provide specifically controlled, accurate delivery of precise quantities of reactants to the process chamber, as a means of improving control over a coating deposition process. The subject matter of the '857 application is hereby incorporated by reference in its entirety. The focus of the present application is the control of process conditions in the reaction chamber in a manner which, in combination with delivery of accurate quantities of reactive materials, provides a uniform, functional coating on a nanometer scale. The coating exhibits sufficient uniformity of thickness, chemical composition and structural composition over the substrate surface that such nanometer scale functionality is achieved.